It has been known for some time that irradiation of cellulose leads to relatively well-defined free radical formation. See, for example, J. C. Arthur, Jr., T. Mares, and O. Hinojosa, Textile Res. J., 36, 630 (1966). But even prior to such structural studies of cellulosic free radicals their chemistry had been utilized to form graft copolymers of cellulose and various monomers using different forms of irradiation (e.g., gamma, X-ray, and ultraviolet) as well as redox systems to generate the cellulose radicals as chain initiators. A comprehensive discussion may be found in an article by E. H. Immergut, "Encyclopedia of Polymer Science and Technology." Volume 3, pp. 242-284, Interscience, 1965.
The particularly careful work of Harris, Arthur, and Carra, J. App. Polymer Sci., 22, 905 (1978) demonstrates some characteristics of particular interest here. Using irradiation absorbed only by cellulose, thereby minimizing homopolymer formation to under about 2%, from 18-72% by weight of glycidyl methacrylate could be grafted onto cellulose. The grafted poly(glycidyl methacrylate) was distributed throughout the cross section of the fibers, but tended to be more concentrated on their outer surface. These workers also found that many other vinyl monomers could be similarly grafted to cellulose.
Graft copolymerization of vinyl monomers onto cellulosic fibers by redox generation of chain initiation is exemplified by the work of Ranby and Gadda, Amer. Chem. Soc. Symp. Ser., 187, 33-43 (1982), who used manganic ions, Mn(III), as the initiator.
In the context of the present application the formation of graft copolymers of cellulose is important as a means of functionalizing cellulose, i.e., modifying cellulose so that the resulting product becomes chemically reactive, especially toward biologically active materials. Other means of functionalizing cellulose have long been known, as for example, conversion of cellulose to carboxymethylcellulose where carboxyl groups are introduced as functional groups, and conversion of cellulose to contain amino-substituted aromatic groups, with subsequent formation of a diazotized cellulose derivative. For convenience as well as conceptual distinction the two kinds of functionalized cellulosics will be referred to as graft copolymers (where the functional group is introduced by graft copolymerization) and as derivatives (where the function group is introduced by a monomeric reagent chemically bonded to cellulose).
Functionalized cellulosics have been investigated in the immobilization of biologically active materials such as enzymes and antimicrobials. Simionescu and Dumitriu (Polymer Sci. Technol., 23, 115 (1983)) explored several cellulose derivatives for immobilization of enzymes via covalent bonding of the functional group of the derivatized cellulose with the enzyme. Antibiotics also were immobilized by covalent bonding to cellulose modified with diazotized amino aromatic groups by reaction of the antibiotic with the diazonium group. However, poly(acrylic acid) grafted cellulose was used to immobilize antibiotics only via ionic bonds, i.e., salt formation accompanying ion exchange. In somewhat related work 6-aminopenicillinic acid (idem., ibid.) and ampicillin (Simionescu and coworkers, Chem. Abst., 100, 215393z), were covalently bound via their amino groups to Biozan R, a xanthan gum having free carboxyl groups (Merck Index, 9th Ed., Merck and Co., Rahway, N.J., p. 1297; U.S. Pat. No. 4,352,882), in the presence of water-soluble carbodiimides as condensing agents.
Other functionalized fabrics also have been used to immobilize biologically active materials. For example, polyacrylate has been irradiation grafted onto hydrolyzed nylon and subsequently hydrolyzed to afford a polyamide-poly(acrylic acid) graft copolymer. Both bovine serum albumin and acid phosphatase were immobilized on the latter using a water-soluble carbodiimide as a condensing agent. C. G. Beddows, J. T. Guthrie, and F. I. Abdel-Hay, Biotech, Bioeng., 23, 2885 (1981).
As previously mentioned, irradiation of cellulose is a general method of generating radicals which initiate polymerization of monomers, thereby leading to graft copolymers. Processes using irradiation are not new to industry and are being utilized increasingly in diverse applications. J. Silverman, J. Chem. Educ., 58, 168 (1981). Particularly cost effective is electron beam technology, which is capable of many variations to best fit the desired application. R. Kardashian and S. V. Nablo, Adhesives Age, December, 1982, 25-29. In electron beam technology a flux of electrons whose energy is in the kilo electron volt range impinges on material passing through the electron beam. Collision of the energetic electrons generally causes secondary electron emission from the material, thus creating a multiplicity of free radical centers. One feature of electron beam technology of particular value here is its indiscriminate nature, i.e., the technology can create free radical centers in virtually all organic materials. Another feature of electron beam technology of interest here is that the depth of electron penetration is a function of electron energy, i.e., the lower the energy of the electron beam the less its penetration, and the more free radicals tend to form at or near the surface of the material rather than throughout its bulk. Yet another feature is that the number of free radicals formed in organic material is controlled by the flux of the electron beam, or exposure time of the material to the electron beam of a given flux, or some combination of the two. The latter three features make electron beam technology a powerful tool in creating a variable number of radical centers in virtually all organic materials while controlling the cross sectional distribution of such centers.
In fact, electron beam initiated graft polymerization of N-vinylpyrollidine on a nylon fabric has been described by Magat et al., U.S. Pat. No. 3,670,048, who then complexed iodine to the graft polymer to obtain fabrics with germicidal properties arising from the slow release of iodine, or who reacted the graft polymer with an alkyl halide to obtain a fabric having a multiplicity of quaternary ammonium sites which imparted an antiseptic effect arising from its being a surface active agent (i.e., detergent). Such antiseptics exhibit non-specific, indiscriminate activity and often are more harmful than helpful in wound healing.
The work of McCormick, U.S. Pat. No. 4,267,280, and Mustacich et al., U.S. Pat. No. 4,343,788, may be briefly mentioned in passing, although neither are considered prior art for the purpose of this invention for both teach a controlled and sustained release of pesticides and carboxylate materials, whereas our invention relies on an antimicrobial remaining firmly bound to the fabric, i.e., our product is characterized by the absence of release or diffusion of an antimicrobial. In McCormick, pesticides are covalently bound to pendant groups of a polymer with the linkages slowly hydrolyzed to release pesticides at a controlled rate. Mustacich teaches the incorporation of carboxylate antimicrobial agents into certain polymers which allow diffusion of such agents from devices fashioned from said polymers to provide a sustained release of antimicrobial agent.
Analogy of our product to an immobilized enzyme also is quite limited. An immobilized enzyme may be active if the substrate can reach the active site by diffusion. However, in our invention it appears necessary that the bound antimicrobial agent not merely contact the microorganism but penetrate its cell wall or outer membrane. The requirements of the underlying immobilizing system affording an expression of antimicrobial activity appear much more stringent and certainly are only poorly understood.
It would appear most desirable for antimicrobial fabrics to have the antimicrobial largely on their surface rather than in their bulk, both for the purpose of maximizing the availability of the antimicrobial as well as minimizing changes in the physical properties of the resulting fabric. It has been known for some time that graft copolymers of cellulose can have the copolymer in the bulk and on the surface of the fiber, and that the relative distribution of the copolymer can be altered and controlled to some extent. By varying the voltage of the electron beam it may be possible to maximize free radical generation at or near the surface leading to maximization of the graft copolymer at or near the surface. By varying the flux of the electron beam it may be possible to vary the extent of graft copolymer formation, thereby leading to optimization of subsequent antimicrobial loading. And since electron beam generation of free radicals is virtually uniformly applicable to organic materials it may be possible to be used in preparing antimicrobial fabrics regardless of the chemical nature of the fabric.
The invention herein is a general method of making antimicrobial fabrics by covalently bonding an antimicrobial to a graft copolymer of a fabric, especially a cellulosic fabric, where the copolymer has a first functional moiety reactive toward a second functional moiety of the antimicrobial. Where the graft copolymer is prepared using electron beam processing there is the advantage that the concentration of the antimicrobial at or near the surface may be varied by altering the copolymer cross sectional distribution via variation in energy of the electron beam. Furthermore, the use of electron beam technology in graft copolymer preparation may be advantageous in controlling the concentration of bound antimicrobial by affecting the amount of copolymer formation via variation of electron flux. Electron beam processing may have additional advantages in its general utility, i.e., virtually any organic fabric should be capable of forming a graft copolymer.
Binding an antimicrobial to a fabric having a copolymer grafted thereto also has certain advantages irrespective of the method of graft copolymer preparation. Because the antimicrobial is covalently bonded to a functional group of the repeating unit in the copolymer, at least a substantial portion of the antimicrobial will be far from the surface of the fabric and therefore not subjected to undesirable surface effects. Another advantage arises from the copolymer containing many such functional groups in the chain, leading to multiple binding of the antimicrobial to each copolymer chain. This can afford rather high antimicrobial loading where desirable, and offers a means to control antimicrobial loading in any case. Yet another advantage of multiple binding sites on the copolymer chain is the possibility of binding several different antimicrobials along the chain, thereby constructing a "broad spectrum" antimicrobial fabric, i.e., one effective against a broad spectrum of microorganisms.